Similar to other encapsulated bacterial pathogens, anti-capsular polysaccharide antibodies confer immunity to diseases caused by Neisseria meningitidis. Group A meningococcal diseases have a different epidemiology than the other pathogenic serogroups. In Africa, Group A meningitis is endemic with high frequency; in other parts of the world, Group A causes epidemics. In both situations, asymptomatic carriage of Group A meningococci is low. In the U.S., disease or carriage of Group A meningococci can be considered as absent for the past 30 years. Yet, most children and young adults throughout the world have Group A polysaccharide antibodies. During investigations to find cross-reactive polysaccharides among non-pathogenic normal flora that might account for this ubiquitous "natural" immunity, two Escherichia coli capsular polysaccharides, K93 and K51, were discovered and their serological properties and structures characterized. Despite their antigenic cross-reactivity, the K93 and K51 failed to absorb Group A antibodies from pre and post immunization sera of vaccinates injected with Group A meningococcal vaccine. Importance of the 0-acetyl in the K93 polysaccharide in this cross-reactivity was established. Schemes for synthesis of K93, K51 and Group A polysaccharides with medically useful carrier proteins have been devised in order to prepare conjugates for clinical evaluation. Such products should be more effective immunogens against Group A meningitis in infants and children than Group A vaccine. A patient, without malignancy and with high levels of a monoclonal antibody reactive with both Group B meningococcal and E. coli K1 capsular polysaccharides, was discovered. The specificity and protective effects of this monoclonal antibody were characterized. Its therapeutic effect in the treatment of Group B meningococcal meningitis is planned to be studied.